Apparatus, methods and computer-accessible media for in situ three-dimensional reconstruction of luminal structures

ABSTRACT

An apparatus for determining a shape of a luminal sample including: a catheter including a lens, the catheter disposed within a strain-sensing sheath such that the lens rotates and translates; a structural imaging system optically coupled to the catheter; a strain-sensing system optically coupled to the catheter; and a controller coupled to the strain-sensing system and the structural imaging system. The controller determines: a first position of the catheter relative to the luminal sample at a first location within the strain-sensing sheath; a second position of the catheter relative to the luminal sample at a second location within the strain-sensing sheath; a first strain of the strain-sensing sheath at the first location; a second strain of the strain-sensing sheath at the second location; a local curvature of the luminal sample relative to the catheter; a local curvature of the catheter; and a local curvature of the luminal sample.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication Ser. No. 62/475,304 filed on Mar. 23, 2017, and entitled“Apparatus, Methods and Computer-Accessible Media for in SituThree-Dimensional Reconstruction of a Luminal Structure,” which isincorporated by reference herein in its entirety.

FIELD OF THE DISCLOSURE

The present disclosure relates to three-dimensional imaging andreconstruction, and more particularly to exemplary embodiments ofapparatus, method, and computer-accessible media for imaging ofcylindrical structures, and even more particularly, e.g., for imagingluminal structures in the human body such as the vascular system andgastrointestinal tract.

BACKGROUND INFORMATION

True three-dimensional (3D) reconstruction is a desirable feature forseveral applications such as measurement of endothelial sheer stress(ESS) to diagnose progression of coronary artery disease and to diagnosesleep apnea in the airway lumen. 3D anatomical structures of the airwayshave been successfully reconstructed with the use of magnetic sensors.However, the large size of magnetic sensor catheters has forcedcardiologists to rely on biplane angiography images to reconstruct the3D shape of the coronary artery. Intravascular ultrasound (IVUS) imagingand biplane angiography have been applied in some studies to calculateESS; however, the repeated use of angiography is often not desirablebecause of complications such as the ionization capability of X-raysused in this process. Additionally, ESS measurements are obtainedthrough a labor-intensive and time-consuming post-processing procedure,making it unsuitable for on-line applications. Another approach todetermining the 3D shape of an artery proposes to use a shape-sensingcatheter that employs optical frequency domain reflectometry (OFDR) witheither multiple fibers or a single fiber with multiple cores thatcontains distributed fiber Bragg gratings. This technique requiresadditional optical fibers that would increase the diameter of thecatheter and make the rotary junction and imaging system morecomplicated.

There is a need to find alternative minimal invasive technologies havinghigh resolution imaging and 3D reconstruction capabilities.

SUMMARY OF THE INVENTION

Optical coherence tomography (OCT) has emerged as a new imaging modalitywhich provides images similar to IVUS but with much higher resolution.When applied to luminal structures, OCT obtains high resolution imagesof the surface and underlying structures of the lumen. However, OCT doesnot provide the overall three-dimensional shape of the lumen andtherefore another methodology is desired which can provide informationto accurately reconstruct the 3D shape while providing high-resolutionOCT images of the lumen and microstructure. Recently, carbonnanotube-based composite coatings have been used to measure strain inmaterials. Accordingly, this technique may be applied to the measurementof 3D shape by measuring local strain-induced spectroscopic informationfrom a carbon-nanotube based strain sensor, which is related to thecurvature of the sheath that is typically used to house an OCT catheterduring intraluminal imaging. Such a strain-sensitive OCT that measuresits own shape is employed in various embodiments disclosed herein inorder to circumvent the time-consuming process of registering theangiogram with intravascular imaging data.

In this invention, a dual channel (e.g. OCT plus strain measurement)system is demonstrated which is capable of measuring the 3D luminalshape while acquiring high resolution cross-sectional images. Thismethod is not limited to coronary arteries and may be applied to obtainthe 3D shape of any luminal or tubular structure, such as other blood orlymphatic vessels, or intraluminal organ including but not limited tothe esophagus, ducts, intestines, ureter, pulmonary airways, pharynx, ora non-biological tubular structures such as a pipe, conduit, tunnel,etc. Furthermore, structural information may be obtained by otherimaging modalities besides OCT (e.g. various embodiments of OCT such aspolarization-sensitive OCT, 1-micron high-resolution OCT, ultrasound,intravascular ultrasound (IVUS) and photoacoustic ultrasound) such asstereo imaging, shape from motion or blurring, computed tomography,x-ray imaging, projection tomography, magnetic resonance imaging, etc.The system and concepts of this work are disclosed herein.

Thus, in one aspect the invention provides for an apparatus including atleast one optical waveguide that emits electromagnetic radiation, ascanning arrangement that at least one of rotates and translates todirect the electromagnetic radiation, a strain-sensing sheath that atleast partially encloses the at least one optical waveguide and thescanning arrangement, the strain-sensing sheath including astrain-sensing system optically coupled to the at least one waveguide;and a controller coupled to the strain-sensing system. The controller,using the strain-sensing system, is to: determine a first strain of thestrain-sensing sheath at a first location, and determine a second strainof the strain-sensing sheath at a second location, the first locationbeing different from the second location. The controller is further to:determine a curvature of the sheath between the first location and thesecond location based on determining the first strain and the secondstrain of the strain-sensing sheath.

In another aspect the invention provides for an apparatus which includesa catheter including a lens, a strain-sensing system, and a controller.The catheter is disposed within a strain-sensing sheath such that thelens rotates and translates within the strain-sensing sheath. Thestrain-sensing system is optically coupled to the catheter. Thecontroller is coupled to the strain-sensing system. The controller,using the strain-sensing system, is to: determine a first strain of thestrain-sensing sheath at a first location, and determine a second strainof the strain-sensing sheath at a second location, the first locationbeing different from the second location. The controller is further to:determine a catheter curvature of the catheter between the firstlocation and the second location based on determining the first strainand the second strain of the strain-sensing sheath.

In yet another aspect, the invention provides for a method whichincludes: providing a catheter having optically coupled thereto astrain-sensing system, the catheter including a lens, the catheterdisposed within a strain-sensing sheath such that the lens rotates andtranslates within the strain-sensing sheath; determining, by acontroller in communication with the strain-sensing system, a firststrain of the strain-sensing sheath in an x-z plane and a y-z plane at afirst location within the strain-sensing sheath; determining, by thecontroller, a second strain of the strain-sensing sheath in an x-z planeand a y-z plane at a second location within the strain-sensing sheath,the first location being different from the second location; anddetermining, by the controller, a catheter curvature between the firstlocation and the second location based on determining the first strainand the second strain of the strain-sensing sheath.

In still another aspect, the invention provides for an apparatus fordetermining a shape of a luminal sample. The apparatus includes acatheter including a lens, the catheter disposed within a strain-sensingsheath such that the lens rotates and translates within thestrain-sensing sheath; a structural imaging system optically coupled tothe catheter; a strain-sensing system optically coupled to the catheter;and a controller coupled to the strain-sensing system and the structuralimaging system. The controller, using the structural imaging system, isto: determine a first position of the catheter relative to the luminalsample at a first location within the strain-sensing sheath, anddetermine a second position of the catheter relative to the luminalsample at a second location within the strain-sensing sheath, the firstlocation being different from the second location. The controller, usingthe strain-sensing system, is to: determine a first strain of thestrain-sensing sheath at the first location, and determine a secondstrain of the strain-sensing sheath at the second location, and thecontroller further to: determine a first local curvature of the luminalsample relative to the catheter between the first location and thesecond location based on determining the first position and the secondposition of the catheter relative to the luminal sample, determine asecond local curvature of the catheter between the first location andthe second location based on determining the first strain and the secondstrain of the strain-sensing sheath, and determine a third localcurvature of the luminal sample between the first location and thesecond location based on determining the first local curvature and thesecond local curvature.

In yet another aspect, the invention provides for a method fordetermining a shape of a luminal sample. The method includes: providinga catheter having optically coupled thereto a structural imaging systemand a strain-sensing system, the catheter including a lens, the catheterdisposed within a strain-sensing sheath such that the lens rotates andtranslates within the strain-sensing sheath; determining, by acontroller coupled to the strain-sensing system and the structuralimaging system, a first position of the catheter relative to the luminalsample at a first location within the strain-sensing sheath;determining, by the controller, a second position of the catheterrelative to the luminal sample at a second location within thestrain-sensing sheath, the first location being different from thesecond location; determining, by the controller, a first strain of thestrain-sensing sheath at the first location; determining, by thecontroller, a second strain of the strain-sensing sheath at the secondlocation; determining, by the controller, a first local curvature of theluminal sample relative to the catheter between the first location andthe second location based on determining the first position and thesecond position of the catheter; determining, by the controller, asecond local curvature of the catheter between the first location andthe second location based on determining the first strain and the secondstrain of the strain-sensing sheath; and determining, by the controller,a third local curvature of the luminal sample between the first locationand the second location based on determining the first local curvatureand the second local curvature.

The foregoing and other aspects and advantages of the invention willappear from the following description. In the description, reference ismade to the accompanying drawings which form a part hereof, and in whichthere is shown by way of illustration preferred embodiments of theinvention. Such embodiments do not necessarily represent the full scopeof the invention, however, and reference is made therefore to the claimsherein for interpreting the scope of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

Further objects, features and advantages of the present disclosure willbecome apparent from the following detailed description taken inconjunction with the accompanying figures showing illustrativeembodiments of the present disclosure, in which:

FIG. 1 is a schematic block diagram of an exemplary embodiment of theapparatus used to reconstruct the 3D shape of a luminal structure;

FIGS. 2A-2D are schematics of exemplary embodiments of opticalstrain-sensing probes employing a single sheath, where FIG. 2A describesthe strain-sensing molecules attached to the exterior sheath wall; FIG.2B describes the strain-sensing molecules attached to the interiorsheath wall; FIG. 2C describes strain-sensing molecules embedded withinthe sheath wall; and FIG. 2D shows an optical strain-sensing probe witha guidewire provision;

FIG. 3 is a schematic of a strain-sensing optical probe with themolecular strain sensors embedded on the exterior of the inner sheaththat is inside of an outer sheath;

FIGS. 4A and 4B are schematics of a strain sensing optical probe wherethe molecular strain sensors are embedded as thin wires that aredisposed on the exterior of the sheath;

FIG. 5 shows an exemplary emission spectrum acquired from a straight,unstrained coronary catheter whose exterior surface was coated withSWCNT;

FIG. 6 provides data related to the wavelength-shift of the emissionspectrum of single-walled carbon nanotubes embedded in a polyurethanecoated intracoronary catheter sheath sampled in-the-plane and orthogonalto the plane of a 45° bend;

FIG. 7 shows a strain-sensing sheath having a bend with a diagram oflight being collected at 0°, 90°, 180°, and 270°;

FIGS. 8A-8C show a series of graphs of peak frequency vs. frame numberas a function of pullback position and rotation angle;

FIG. 9 is a block diagram of an exemplary embodiment of an apparatus forreconstructing the 3D shape of a luminal object such as vessel accordingto the present disclosure;

FIG. 10 is a schematic of the exemplary process for reconstructing thethree-dimensional shape of a luminal object from a combination of OCTand spectroscopic data acquired at a known pullback position androtational angle;

FIG. 11 shows a schematic of the RT-ESS catheter and imaging console.ECG: electrocardiogram; DCF: double-clad fiber; CFO: computational fluiddynamics; HCT: hematocrit; ESS: endothelial shear stress; OCT: opticalcoherence tomography; NIRF: near infrared fluorescence; SWCNT:single-walled carbon nanotubes; Fluor: fluorescence;

FIG. 12A shows fluorescence spectra of (7,5) and (7,6) SWCNT on thecatheter's sheath at 0 (solid line) and 0.08 mm⁻¹ (dotted line)curvatures showing compressive strain-induced blue and red wavelengthshifts, respectively; and FIG. 12B shows a scatter plot of (7,5) and(7,6) peak separations vs. sheath curvature;

FIG. 13A shows 3D geometry of a human right coronary artery lumen thatwas 3D printed to create a physical phantom; FIG. 13B shows a 3D imageof the phantom reconstructed by the SWCNT catheter; and FIG. 13C shows acenterline of a 3D reconstruction relative to X, Y, and Z axes;

FIG. 14 shows a schematic of an RT-ESS console in which: RJ: rotaryjunction; C: circulator; BS: beam splitter; WDM: wavelength divisionmultiplexer; PC: power combiner; REF: reference arm;DB-PD-dual-balanced, polarization-diverse; ADC: analog/digitalconverter; CPU: central processing unit; GPU: graphical processing unit;

FIG. 15 is a flow chart of an example process for determining a shape ofa luminal sample; and

FIG. 16 is a flow chart of an example process for determining a shape ofa catheter disposed within a sheath.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

Thus, disclosed herein is the development of apparatus and methods,including embodiments of instrumentation, probes, and algorithms, tomeasure the three-dimensional shape of a luminal structure, including invivo. The exemplary embodiments disclosed herein are applied tointracoronary imaging and can provide an input to computational modelsthat estimate the endothelial shear stress on the artery wall.Nevertheless, the techniques and apparatus disclosed herein may be usedto determine information about other luminal structures in addition tocoronary vessels.

A particular feature of the present disclosure is that athree-dimensional shape of a luminal structure such as a coronary arterycan be reconstructed using structural data acquired from a structuralimaging system, such as optical coherence tomography, and from astrain-sensing system based upon, for example fluorescence emission ofsingle-walled carbon nanotubes affixed to a sheath. The presentdisclosure may be embodied in clinical instruments, intracoronarycatheters, and methods that may be used to reconstruct the 3D shape of acoronary artery (or other luminal structure) in real-time and furtherthat this input may be used to provide real-time 3D coronary shapes forcomputational fluid dynamics models that estimate endothelial shearstress (ESS) in patients undergoing percutaneous coronary interventions.

Diagnosis and treatment of coronary artery disease (CAD) is hindered byan inability to investigate fundamental pathobiological processes thatlead to coronary atherosclerotic plaque progression and destabilizationin humans. A critical mechanism responsible for plaque behavior is localshear stress experienced by endothelial cells, governed by the geometryof the vessel and, consequently, the local patterns of blood flow. Inregions of low ESS, endothelial cells respond by increasing permeabilityto protein complexes such as LDL and further trigger a variety ofproatherogenic, proinflammatory, and prothrombotic processes at thatsite. This low shear stress milieu is the environment that uniquelydictates a pathobiological endothelial response and atheroscleroticplaque progression/destabilization.

Recently, methods have been developed for computing ESS of humancoronary arteries in vivo. Reconstruction of the 3D anatomy of eachcoronary artery is accomplished by registering intracoronary opticalcoherence tomography (OCT) or intravascular ultrasound (IVUS) imagingdata to specially-acquired angiograms. This 3D anatomic data is theninput into a computational fluid dynamics (CFD) model that computes ESSat the coronary artery's luminal surface. These techniques have now beenused in natural history clinical studies; results show that low ESS isthe most powerful predictor of future coronary events. However, ESSmeasurements cannot currently be obtained in the cardiac catheterizationlab in real-time, as registration of imaging data, 3D reconstruction,and CFD modeling are time-consuming and must be performed off-line. Dueof these limitations, it takes hours to compute the ESS maps for eachartery in any given patient.

Thus, the methods and apparatus of the present disclosure may help toimprove outcomes of patients by enabling real-time ESS (RT-ESS)measurement during routine cardiac catheterization to guide personalizedmanagement of CAD. The simplicity, efficiency, and precision deliveredby the proposed RT-ESS technology provides a significant improvement inthe ability to use ESS information in research and clinical practice.

Accordingly, the present disclosure describes the development of RT-ESStechnology for clinical CAD patient management. A shape-sensing OCT-NIRF(near-infrared fluorescence) imaging catheter and automated imageprocessing algorithms can accurately and rapidly reconstruct thecoronary artery without requiring an angiogram. In various embodiments,the inner surface of the RT-ESS catheter's sheath may be coated withsingle-walled carbon nanotubes (SWCNTs), which have strain-dependent NIRfluorescence spectra. Fluorescence spectra from the sheath can beacquired and analyzed as the catheter's optics are helically scanned,providing the shape (centerline) of the catheter. OCT images of theartery wall, acquired simultaneously with the fluorescence spectra, maybe automatically segmented and mapped to the catheter's centerline toprovide a true 3D representation of the artery's lumen.

In various embodiments, the 3D arterial geometry can be used to generatea 3D mesh for CFD modeling. Using patient-specific blood viscosity andartery-specific blood flow rates, flow simulations can be performed inthe mesh via a highly parallel CPU workstation running a pressure-basedcoupled parallel solver.

A schematic block diagram of an exemplary embodiment of a 3D-shapesensing device with shape sensing probe according to the presentdisclosure is shown in FIG. 1. This exemplary device apparatus caninclude a structural imaging system 110, which generates images of aluminal object's 160 microstructure, a strain-sensing system 120, whichgenerates data from which the 3D shape of a luminal object 160 can bereconstructed, output of the structural imaging system 115, output ofthe strain-sensing system 125, a dual modality rotary junction unit 130,a strain-sensing probe 135 with a sheath 140, a data acquisition system145, and data processing and storage unit 150. It should be understoodthat a plurality of each of these described systems, arrangements andelements can be included and/or implemented in or together with theexemplary apparatus.

The structural imaging system 110 is designed to collect back-reflectedsignals that can be either optical or mechanical in nature from aluminal structure 160 to acquire information regarding the luminalsurface and underlying microstructure. The exemplary structure is tissueand in particular a coronary artery. Depth-resolved microstructuralimages obtained from the structural imaging system 110 can containfeatures related to the probe sheath 140 as well as the luminal surfaceand subsurface.

In the exemplary embodiment, the structural imaging system 110 willimplement optical coherence tomography (OCT) or other OCT-relatedmodalities to produce depth-resolved microstructural images. OtherOCT-related modalities include optical frequency domain imaging (OFDI),polarization-sensitive optical coherence tomography (ps-OCT), and otherembodiments of higher-resolution OCT, also known as μOCT, that canemploy a distal optical design to extend the depth of focus whilemaintaining a sub 10-μm lateral spot size.

In another embodiment, the structural imaging system may implementintravascular ultrasound (IVUS) or photoacoustic ultrasound imaging toinvestigate the tissue microstructure. Similar to OCT, both technologiesproduce transverse images that are automatically registered to strainmeasurements.

The strain-sensing system 120 contains instrumentation and componentsthat can enable either fluorescence spectroscopy, Raman spectroscopy, orabsorption spectroscopy. Localized material strain is encoded in thecentral wavelength of the molecular spectrum. Although instrumentationis specific to the spectroscopic technique used, in general eachspectroscopic technology requires a light source for probing themolecular signature, a dispersing element such as a prism, grating,spectrometer, or spectrograph to separate the returned spectroscopicsignal, and an optical detector to record the molecular signal. In analternative embodiment, the source wavelength may be scanned as afunction of time and similar information may be obtained by detectingthe light spectroscopically without requiring a dispersive element inthe detection path.

While the structural imaging system 110 can be connected to the dualmodality rotatory junction 130 via a single mode fiber 115, thestrain-sensing system 120 can be connected with either a double-cladfiber (DCF) 125 or a combination of single-mode and/or multimode fibers.The dual modality rotary junction 130 can combine two optical beams fromdifferent modalities and serve as an interface between a stationaryimaging platform and a helical scanning (rotation and translation) probe135. Optical beam combining and splitting in the dual-modality rotaryjunction can be accomplished through the use of dichroic mirrors, beamsplitters, or arrangement of dispersive elements. A transparentstrain-sensing sheath 140 may be used to protect the probe 135 and maycontain molecular strain-sensors that report the local curvature of thestrain-sensing sheath 140 during a helical scan of the luminalstructure. Optical beams 155 from the structural imaging 110 andstrain-sensing 120 modalities can be delivered by a double-clad fiberwithin the probe 135 and interrogate the sheath and microstructure of alumen, such as a coronary artery. An advantage of the DCF-based,mechanically-scanning OCT-fluorescence catheter is that the double cladfiber in the probe may be used to simultaneously collect co-localizedand intrinsically co-registered OCT from the lumen and fluorescencelight from the probe's sheath at each scan point. Light reflected fromthe luminal wall and fluorescence emission from the sheath is collectedby the optical probe and transmitted to the dual modality rotaryjunction, where the back-reflected structural (e.g. OCT) light isseparated and returned to the structural imaging system 110 and thespectroscopic signal (i.e. from the strain-sensing sheath 140) isreturned to the strain-sensing system 120 for spectral analysis anddetection. The resulting structural (e.g. OCT) and spectroscopic data isrecorded by a data acquisition system 145 and these signals are analyzedand processed to reconstruct the three-dimensional shape of the luminalstructure by a data processing and storage unit 150.

Exemplary schematics of several strain-sensing sheaths designed for aside-viewing multimodality optical probe are presented in FIGS. 2A-2D.FIG. 2A describes an embodiment of a strain-sensing sheath 200 in whichthe strain-sensing molecules can be located on the exterior sheath wall.The dual modality optical probe includes an optical fiber 202 thattransceives broadband light from the structural imaging system 110 andexcitation light from the strain-sensing system 120. The distal end ofthe optical fiber is terminated with optics 204 that focus and collectthe OCT and spectroscopic signals. The preferred optical fiber 202 usedin the present embodiment is a double-clad fiber (DCF). The structure ofa double-clad fiber incorporates a central core surrounded by an innerand outer cladding. The core is designed to transceive single-mode lightwhile the inner cladding collects light similar to a multimode fiber.Structural imaging light (e.g. OCT) is transceived by the single modecore while the excitation light can be focused into either the core orinner cladding of the DCF while the returned emission light is collectedby the inner cladding. The double-clad fiber 202 is threaded through atorque-transmitting driveshaft 206 and this assembly is then threadedinto a thin-walled flexible sheath 208 that will conform to the shape ofthe luminal structure. In the embodiment of FIG. 2A, molecular strainsensors 210 are applied to the exterior of the sheath 208, which is indirect contact with the luminal structure (e.g., tissue). The materialsof the sheath 208 and exterior coating/strain sensors 210 are chosen tobe optically transparent to the broadband OCT light and spectroscopicsignals. In preferred spectroscopic embodiment (e.g. fluorescence),excitation light is focused by the distal optics 204 and excites themolecular strain sensors, which emit red-shifted light that is collectedby the distal optics and guided by the optical fiber 202 to the rotaryjunction 130, which separates the optical signals and sends them totheir respective structural optical 110 and strain-sensing 120 systems.

FIG. 2B presents an exemplary schematic of another embodiment of astrain-sensing optical probe 220 in which the molecular sensors 210 areapplied to the interior wall of the sheath 208. This is a preferredembodiment since the molecular sensors are isolated from the luminalsurface by sheath material thereby avoiding direct contact with thelumen (e.g. tissue and fluids). In the ideal case, the coatingcontaining the molecular sensors is thin, to accommodate free, uniformrotation of the driveshaft. FIG. 2C presents another exemplary schematicof yet another embodiment of a strain-sensing optical probe 230 in whichthe molecular sensors are embedded in the sheath materials at the timeof sheath extrusion. A second polymer that does not contain molecularsensors may be coextruded outside of the inner strain-sensing polymer toisolate the lumen (e.g. tissue and fluids) from direct exposure to thesensors. As shown in FIG. 2D, any of the disclosed embodiments(including those in FIGS. 2A-2C, 3, and 4A-4B) may include a guidewireprovision 252 including a guidewire path (with openings 254 and 256 forentry and exit of a guidewire). In addition, the guidewire provision 252may include a radiopaque tip marker 258 to help locate the probe 200 ina subject using for example fluoroscopy. Furthermore, each of theembodiments (including those in FIGS. 2A-2C, 3, and 4A-4B) mayoptionally include a radiopaque lens marker 212 as shown in FIG. 2D tohelp locate the probe 200 in a subject using for example fluoroscopy.

A second exemplary embodiment of strain-sensing optical probe 300 ispresented in FIG. 3. In this embodiment, a second smaller diameter innersheath 302 is coated with strain-sensing molecules 210 and can then bethreaded inside of a larger exterior sheath 208. The opticalfiber/driveshaft assembly is then threaded into the smaller diametersheath 302. This embodiment has the advantage that it does not alter theproperties of the exterior sheath 208.

Accurate reconstruction of the 3D shape of a luminal structure dependsupon the uniform rotation and pullback of driveshaft through thestrain-sensing sheath. Non uniform rotational distortion (NURD) cannegatively impact the 3D reconstruction. Corrections for NURD ortorsion-induced fluorescence can be identified and corrected by adding afiducial marker to the sheath that can be detected by both modalities.In a third exemplary embodiment of a strain-sensing sheath, strainsensing molecules can be incorporated in thin threads or wires 402 thatare themselves embedded in the sheath, as presented in FIGS. 4A and 4B.FIG. 4A shows a cross-sectional side view and FIG. 4B shows across-sectional end view of the optical probe 400. In this particularembodiment, four sensing wires 402 are embedded within the sheath at 90°radial locations from each other. In the preferred embodiment, the wirescoated with strain-sensing molecules can be embedded in the sheath 210during the extrusion process. In another embodiment, the strain-sensingwires 402 can be attached to the exterior of the sheath 210 and sealedin place by a polymer over-sheath or a thin application of curablepolymer materials. In various embodiments, fewer than four wires orgreater than four wires may be used; generally the wires are equallyspaced around the outer circumference of the sheath.

Molecular strain sensors are molecules or macromolecules whoseelectronic structure changes predictably in response to changes in thestrain of the host material as it undergoes compression or stretching.An exemplary strain-sensing material is single-walled carbon nanotubes(SWCNTs). SWCNTs are a class of nanoscale tubes composed completely ofcovalently-bonded carbon atoms. Each SWCNT has a well-defined molecularstructure characterized by a pair of integers (n,m) that specifies thetube diameter and roll-up angle of the SWCNT. The physical structure ofa SWCNT controls its electronic structure, and thus the spectraltransitions that the SWCNT undergoes. Axial stretching and compressionof individual SWCNT results in predictable changes in the electronicstructure, which systematically perturbs the molecular structure andshifts the spectral transition resulting in a frequency (wavelength)shift in the fluorescence, absorption, or Raman spectrum when thenanotube is strained. It has been established in the literature that thedirection of the strain-induced spectral shift occurs in oppositedirections for SWCNT of different modulus (n-m,3). For example, the peakemission wavelength shifts in the fluorescence spectra can be largeenough to detect axial strains as low as 0.1% in some embodiments.

In an exemplary embodiment 200, a coating 210 containing SWCNT may beapplied to the exterior of a coronary catheter sheath 208 as shown inFIG. 2A. The strain-sensing coating was prepared by dispersingsingle-walled nanotubes grown via the CoMoCAT process in a mixture ofpoly(9,9-di-n-octylfluorenyl-2,7-diyl) (PFO) and toluene. The solutionwas tip-sonicated at 1 W/ml for 30 minutes and followed bycentrifugation for 30 minutes. The clear supernatant containing theisolated nanotubes was removed. As per the literature, the solubility ofnanotubes is low in nearly all solvents. The strong non-covalentinteractions between PFO and SWCNT resulted in single-wrapped nanotubesthat isolate chiralities (7,5) and (7,6). After centrifugation, theclear solution containing enriched (7,5) and (7,6) nanotubes was mixedwith a commercially-available oil-based polyurethane (Minwax FastDryingSemiGloss Polyurethane) at a ratio of 1:1. The exterior of a coronarycatheter sheath 208 was dip-coated in the SWCNT-polymer solution andallowed to cure. Multiple layers may be deposited along the 10-cm-longdistal segment to optimize the fluorescence signal. In this exemplarycoating, the average coating thickness of 36 μm varied by only±6 μm. Dueto the thin coating, the catheter sheath maintained its flexibility towithin 5% as assessed by a standard gravity-induced deflection test.

In another exemplary method to achieve high concentrations ofindividually dispersed (7,5) and (7,6) nanotubes, single-chiralityseparation and purification may be achieved by suspending the nanotubesin a aqueous solution of sodium dodecyl sulfate (SDS) and usingultrasound sonication. After sonication, SWCNT suspensions may beultracentrifuged to remove aggregates and the SWCNT solution may besubjected to multistage gel chromatography. With this method, theconcentration of nanotubes in solution can be on the order of 1 μg/ml,which can be several orders of magnitude above that used for theexamples disclosed herein. The enriched nanotube solution can be mixedwith a curable polymer coating according to embodiments 200, 220, and230 or mixed into a polymer feedstock prior to extrusion according toembodiments 300 and 400.

An exemplary emission spectrum acquired from a straight, unstrainedcoronary catheter whose exterior surface was coated with SWCNT 200 isdisplayed in FIG. 5. Fluorescence excitation light at 660 nm was coupledinto the optical core of the double-clad fiber 201 and focused onto theSWCNT-coated sheath by an angle-polished ball lens 202 positioned at theend of the dual clad fiber. Fluorescence emission from the nanotubes wascollected through the inner cladding of the same double-clad fiber 201and focused into an optical spectrometer equipped with a linear InGaAsarray detector. The emission spectrum was recorded over the range of950-1170 nm and shows two prominent peaks at approximately 1050 nm(515), and 1135 nm (520) that are attributed to emission from (7,5) and(7,6) nanotubes, respectively; the fitted portions of each peak aredelineated by horizontal tick marks. The peak emission wavelength may beaccurately determined by fitting individual emission peaks to a spectralline shape such as log normal 510, Gaussian, or other known line shapefunctions. Single or multiple functions may be needed to represent theacquired line shape. Polynomial fitting may also be used to determinethe peak emission wavelength. Spectral fitting can determine theemission wavelength to subpixel accuracy for the determination of smallstrains.

Exemplary emission spectra acquired from a strain-sensing sheath areshown in FIG. 6. Spectra were acquired every 90° corresponding to theexcitation beam residing in the plane of the bend (0° and 180°) andorthogonal to the plane of the bend (90° and 270°) (see FIG. 7). At theinner curvature (0°), the sheath (nanotubes) experienced a compressivestrain resulting in the spectral emission from (7,5) and (7,6) nanotubesto be shifted to lower (blue-shifted) and higher (red-shifted)wavelengths, respectively. At the outer curvature (180°), the sheath wasunder tensile strain, which resulted in the spectral emission shiftingin the opposite direction for (7,5) and (7,6) nanotubes. Spectraacquired in the orthogonal, out-of-plane angles (90° and) 270° werenearly identical and with no appreciable shift in the emissionwavelength.

The fluorescence spectra from a strain-sensitive sheath were acquired asthe probe helically scanned a sheath that followed a well-defined bendradius. Emission spectra were spectrally fit to a line shape function todetermine the peak emission wavelength as function of pullback positionand rotation angle as shown in the exemplary data in FIGS. 8A-8C. Theframe number (shown on the horizontal axis) is a function of thepullback distance and rotation angle. The extracted emission wavelengthsfor chiralities (7,5) and (7,6) are shown in FIGS. 8A and 8B,respectively, and their difference (7,6)-(7,5) is shown in FIG. 8C. Inthe first 200 frames, the coronary catheter is relatively straight,showing little rotational variation in the emission wavelength duringscanning. At approximately frame 400, the catheter experiences aconstant bend radius of 12 mm, producing a periodic function whose peakwavelength extremes cycle between the maximum tensile and compressivestrains. A curvature-dependent wavelength is obtained by averagingseveral cycles.

A calibration curve that relates the spectral shift to nanotubechirality or multiple nanotube chiralities may be constructed byextracting an averaged emission wavelength for either the compressive ortensile strains as a function of curvature. Note that a mathematicalcombination of chiralities may increase the strain sensitivity becausethe strain-induced spectral shifts may act under opposite directionsunder the same stresses, which is observed for the difference betweenemission wavelengths of (7,6) and (7,5). FIG. 12B (discussed below)shows a calibration curve that maps the spectral shift (peak separation)relative to the radius of curvature. As seen in FIG. 12B and discussedfurther below, this relationship is linear and sensitive over a range ofcurvatures that is needed to detect the 3D geometry of the catheter.

FIG. 9 is a schematic of an exemplary embodiment of a three-dimensionalshape sensing system, which is comprised of two subunits: (1) an opticalfrequency domain imaging (OFDI) engine that acquires microstructuralimages of tissue, and (2) a fluorescence engine that provides theshape-sensing capabilities. The OFDI system is built around a SweptSource Engine from AXSUN Technologies. In addition to a 100 kHz sweptlaser, the OCT Axsun engine contains high-speed data acquisitionelectronics which are optimized for acquisition of OFDI data using anEthernet interface. The swept wavelength light from the Axsun laser iscoupled to a single mode (SM) fiber-based beam splitter (BS1) whichdirects 90% of the signal to the sample arm and 10% to the referencearm. After passing through a circulator (C), the sample arm light iscombined with the fluorescence excitation beam using a wavelengthdivision multiplexer (WDM) unit. The combined excitation and OCT laserbeam is coupled to a double clad (DC) fiber coupler (FC) which isattached to a custom-fabricated rotary junction. A DC fiber catheter isattached to the rotating part of a rotary junction (RJ). At the end ofthe catheter, a ball lens is fabricated and polished to direct the lightsignals towards the sample; in one particular embodiment a custom fibercatheter is placed within a flexible transparent sheath. In certainembodiments the outside of the sheath is coated with carbon nanotubesfor strain sensing, although in other embodiments the strain-sensingmaterial may have a different location (e.g. embedded in the sheathmaterial or on the inside of the sheath). During imaging, the catheteris rotated and the rotating catheter is pulled back within the sheath togenerate helical scans.

For OFDI imaging, back-reflected light from the sample and referencesurfaces is directed by corresponding circulators (C) toward a beamsplitter (BS2) where these signals interfere with each other. The use ofpolarization beam splitters (PBS1, PBS2) and polarization controllers(PC) after the beam splitter BS2 allows implementation of a polarizationdiverse detection scheme that avoids image artifacts that mightotherwise arise due to polarization changes induced by the optical fiberin the rotating catheter. Light from the polarization maintaining (PM)fibers is detected using two balanced detectors composed of four diodereceivers. The digitized signal from the photodiodes is then processedon a field-programmable gate array (FPGA) board including wavelengthre-mapping and Fourier transformation to obtain a depth-resolved OFDIsignal (A-line). A-lines collected during every rotation of the opticalbeam are compressed by the Axsun engine to a JPEG format and transferredto a workstation via an Ethernet cable for real-time circumferentialdisplay and data storage.

On the strain sensing side, the fluorescence signal from the carbonnanotubes is collected through the cladding of the DC fiber of thecatheter. After passing through the RJ, this signal is sent to thespectrometer by the fiber coupler. In one embodiment, the spectrometerincludes an input slit, guiding optics, a grating, and a super-cooled,low noise linear response camera. The signal from the spectrometer isused to determine the strain within the sheath.

FIG. 10 describes the algorithm for 3D reconstruction using one of theexemplary embodiments. In various embodiments, full 3D reconstruction isbased on input from two channels, namely a structural optical (e.g.OFDI) imaging channel and a strain sensing channel. First, the positionof the catheter with respect to the artery wall is determined eithermanually, or semi-automatically or automatically using image analysisalgorithms to detect said position, at two different locations, Z1 andZ2, in two different planes, x-z and y-z. Using these values, thecurvature of the catheter with respect to the artery wall is calculated.Further, using the fluorescence data from carbon nanotubes, strain iscalculated in the same planes (x-z and y-z) as curvature was calculatedfrom OFDI data, and the measured strain values are converted tocurvature using the calibration data. This process gives the curvatureof the catheter itself in two planes. The actual curvature of the arteryin different orthogonal planes can be calculated by adding the curvatureof the catheter and the curvature of the artery with respect to thecatheter in these planes. Once the curvature of the artery is known intwo planes, the 2D shape is calculated in the orthogonal planes. The 3Dshape can be generated from the shapes in the two orthogonal planesusing software such as the commercially-available IVUSAngio tool.

The process of measuring ESS from these data is extremelytime-intensive, necessitating a unique catheterization lab process andbiomedical engineering expertise. The angiogram must be acquired using abiplane/isocentric configuration so that the artery can be accuratelyreconstructed in three dimensions, a requirement that is impractical formost PCI labs. 3D reconstruction is laborious, as the artery'scenterline must be derived from the angiogram, the OCT or IVUS lumenssegmented, and the lumen centroids co-registered to the centerline. Thepresent disclosure provides methods and apparatus to bypass resource-and time-intense limitations of ESS computation by providing a singledevice that can automatically and in real-time determine the 3Dstructure of the arterial lumen, calculate the detailed local ESSpatterns, and display them in concert with anatomic characterization byOCT. By removing the barriers to ESS computation and providing apractical means for obtaining this measurement in real-time or nearreal-time in the catheterization lab, this advance can make it possiblefor the first time to use ESS to guide coronary intervention and provideoptimal CAD management at the point of care.

These data may be processed to automatically determine the 3D centerlineof the catheter. In combination with automated luminal segmentation,this technology can allow the luminal contours to be rapidly mapped tothe catheter's centerline to reconstruct an anatomically correct 3Drepresentation of the coronary artery.

FIG. 11 depicts a high-level schematic of an embodiment of an RT-ESSsystem and catheter. In some embodiments, the catheter may be identicalto an existing clinical 2.6 F intracoronary DCF-based OCT-NIRF catheterand, in particular embodiments, the inner surface of the outer sheathmay be functionalized with a thin layer of fluorescent SWCNTs for whichthe emission spectra are shifted when placed under strain. OCT (1310±50nm) and SWCNT fluorescence excitation light (660 nm) can be transmittedthrough the core of the DCF within the multimodality catheter. Underradiographic guidance, the catheter may be advanced over a guide wirethrough a guide catheter until its imaging tip is located distally tothe target coronary location. A non-occlusive radiocontrast flush can beinjected through the guide catheter, displacing blood from the artery'simaging field. Light from the focusing optics at the distal tip of thecatheter can then be helically scanned via a high-speed DCF rotaryjunction (in one embodiment the rotation rate may be 800 kHz and thetranslation rate in a range of 10-20 cm/s), gated to diastole viasynchronization with real-time ECG. OCT light from the artery wall willreturn through the DCF's core. NIR SWCNT fluorescence (1000-1200 nm)from the entire catheter's sheath can be simultaneously collectedthrough the DCF's larger inner cladding. OCT and fluorescence light maybe separated inside the RT-ESS console and detected and digitizedseparately. OCT images may be automatically segmented to extract eachcross-section's lumen. Automated processing of the peak shifts in theSWCNT fluorescence spectra will determine the catheter's 3D centerline.An anatomically correct 3D artery model will then be reconstructed byplacing the lumens onto the intrinsically co-registered catheter'scenterline. To compute artery-specific flow, a known volume of contrastcan be injected through the guide catheter and while acquiring anotherOCT scan. The time between OCT images of the leading and trailing edgesof the bolus can then be used to estimate blood flow. Blood viscositycan be determined from the patient's hematocrit (HCT). The 3D arterymodel, blood flow, and blood viscosity may be input into a highlyoptimized, parallel CFD simulation, the output of which can provide anESS map.

In certain embodiments, OCT is employed as the intravascular anatomicimaging technology because it is a standard imaging technique forassessing plaque morphology and the adequacy of stent deployment in thecatheterization lab. Furthermore, its high resolution and contrast canprovide the most accurate geometry and detailed ESS maps. Because OCTimages are acquired with a non-occlusive radiocontrast flush to removeblood from the field of view, such images are also very amenable forautomated analysis. A recent study has shown that OCT measures of plaqueextent and free wall arc are highly correlated to IVUS measures ofplaque burden, which is significant because this metric is associatedwith future coronary events.

The fluorescence spectra of a catheter having a strain-sensitive sheath(made by applying SWCNTs to the sheath as described above) coupledthereto were measured at various curvatures to determine therelationship between curvature and SWCNT fluorescence peak separation,as shown in FIGS. 12A-12B. Fluorescence excitation light (660 nm) wascoupled into the catheter's DCF core and focused onto the coated sheathby an angle-polished ball lens at the end of the fiber. Fluorescenceemission from the nanotubes was collected through the inner cladding ofthe DCF and detected by a spectrofluorometer. FIG. 12A (solid line)shows the fluorescence spectrum of the (7,5) and (7,6) SWCNT coating ona straight catheter, demonstrating two NIR emission peaks atapproximately 1050 nm and 1140 nm, respectively. The catheter was thenbent and its optics were directed to collect fluorescence in-plane withthe bend from the inner curvature of the sheath. At this location, thenanotubes experienced compressive strain, causing the fluorescent peaksto broaden and spectrally shift away from one another (FIG. 12A, dottedline). Opposite shifts occurred for tensile strain (not shown). The(7,5) and (7,6) peak separations were measured as a function of varyingsheath curvatures by fitting the individual peaks with a Gaussian lineshape function. As seen in FIG. 12B, this relationship was linear andsensitive over a range of curvatures that is needed to detect the 3Dgeometry of the catheter. This data shows that carbon nanotubefluorescence can be used to detect the curvature of the RT-ESS catheter.

SWCNT Catheter-Based Shape Sensing and 3D Artery Reconstruction

To test the principle of SWCNT catheter-based shape sensing for 3Dreconstruction of a coronary artery, the aforementioned catheter wasconnected through a DCF rotary junction to an OCT-NIRF system, modifiedby the addition of custom wavelength-separating optics and NIRfluorescence spectral detection. The catheter was then inserted into aphantom of a coronary artery lumen, which was 3D-printed using a lumencenterline from a human dataset (FIG. 13A). The catheter's inner opticswere helically scanned along the phantom's lumen (1 mm/s pullback and 1Hz rotation), simultaneously grabbing OCT A-lines and fluorescencespectra from the catheter's sheath at every angular (θ) and lateral (z)location. The OCT dataset was processed by segmenting the lumen. Thefluorescence spectra were fit and peak separations were used to create acurvature map at each 0-z scan position. The catheter's curvature mapwas converted to a 3D catheter centerline by solving modifiedFrenet-Serret equations. The OCT lumens for each frame were subsequentlysuperimposed on the catheter's centerline, converted into a 3D mesh, andrendered (FIG. 13B). The 3D centerline of the phantom artery's lumenmeasured using the SWCNT catheter (FIG. 13B) closely matched the known3D centerline of the phantom, with a Pearson's Correlation Coefficient(PCC) of 0.84. FIG. 13C shows a centerline of the 3D reconstructionrelative to X, Y, and Z axes. This data shows that OCT-NIRF and a SWCNTcatheter can be used to automatically and accurately measure the 3Dshape of a coronary artery.

SWCNT Fluorescence Efficiency

To recover the shape of the catheter, embodiments of a clinical RT-ESSsystem may need to acquire at least 8 spectra per circumferential scanof the catheter's optics. Assuming a frame rate of 800 Hz, spectra willbe digitized at approximately 6.5 kHz (150 μs integration time), whichmay be facilitated by the use of a high-speed imaging spectrograph.Using relatively crude and low concentration SWCNT preparations, anadequate fluorescence signal strength of 2000 counts has been achievedduring a 100 ms integration time with 10 mW of optical power on thesheath. Applying an SNR analysis and assuming a safe excitation power of50 mW, in various embodiments an approximately 100-times higher SWCNTfluorescence intensity may be needed to facilitate faster acquisitionrates, a factor that may be gained by increasing nanotube concentrationand alignment as described further below. These results show thefeasibility of achieving the SWCNT fluorescence intensity required tomeasure the catheter's shape at RT-ESS acquisition rates.

Although data disclosed herein demonstrates that a SWCNT-functionalized,mechanical scanning OCT catheter can create accurate 3D coronary arterymodels, in various embodiments an improved device suitable for use inhumans may be provided. In one embodiment, nanotubes may be coated onthe inside of the sheath to shield the SWCNT from body fluids, althoughdoing so may be challenging when the catheter includes a closed distaltip. In other embodiments, the nanotubes may be coated at higherconcentrations than used in the example above; the nanotubes may bedispersed to maintain their fluorescence properties; and the nanotubesmay be aligned along the catheter's axis to optimize emission intensityand strain sensitivity. In further embodiments, the coating may be thin,tightly-toleranced, and robust so that it is not effaced by the rotatingdriveshaft.

In various embodiments, the RT-ESS console may be capable of one or moreof: 1) acquiring high speed OCT images; 2) detecting and digitizingSWCNT fluorescence spectra; and 3) rapidly processing these signals tocompute ESS. The target time from acquiring the OCT data to ESS may be 1minute (optimal) to 3 minutes (minimal), either of which is asufficiently short time that it can be completed during acatheterization lab procedure. FIG. 14 shows a schematic of anembodiment of a RT-ESS console.

OCT light may be provided by a wavelength-tuned laser that uses aMEMS-based Fabry-Perot cavity to sweep over a ˜100 nm bandwidth at 200kHz A-line rate with a duty cycle of 50%. To acquire cross-sections at800 Hz (512 A-lines/image), the A-line frequency may be doubled to 400kHz by buffering (2×) the laser using a fiber optic delay lineterminated by a Faraday mirror. A buffer optical amplifier may beutilized to normalize output power. The OCT interferometer may use astandard circulator-based Mach-Zehnder configuration with acomputer-controlled reference arm path length. 660 nm SWCNT excitationlight can be combined with OCT sample arm light through a WDM; both maythen be coupled to the core of a DCF via a power combiner.

Fluorescent light from the sheath returning through the DCF's innercladding may be diverted through the power combiner to a MMF that willilluminate a high-speed NIRF (6000 spectra/s) InGaAs imagingspectrograph. The OCT spectral interferometric signal can be detectedusing a dual-balanced polarization diverse detection unit. Detectoroutput may be digitized at 12 bits, sampled by a doubled k-clockprovided by the laser. Interferometric OCT data may be transferred to aGPU, converted into OCT images, processed, displayed, and stored tohigh-speed solid-state drives (SSDs).

In various embodiments, a rotary junction such as that used withmultimodality DCF-based devices, the use of which has been demonstratedclinically, may be used. To avoid motion artifacts in the OCT dataset,image acquisition and catheter rotational rates may be increased so thatthe entire pullback can be accomplished during a single diastolic cyclewhen the catheter and artery are stationary. Initiation of thecatheter's helical scan may be synchronized to the diastolic trigger ofa real-time ECG recording. Assuming a maximum heart rate of 100 bpm, andgiven that diastole is ˜50% of the cardiac cycle, an average 5 cmpullback may take ˜0.3 s. Given an image spacing of 200 μm, 250 imagesmay be captured in 0.3 s, requiring a rotational rate of ˜800 Hz.

Acquired spectra may be fit to a Gaussian function to determine (7,5)and (7,6) SWCNT fluorescence peak separations, which can be converted tocurvature at each 0-z scan position. The centerline may be computed bysolving Frenet-Serret equations describing the 3D catheter's path.

Thus, in various embodiments the invention includes an apparatus fordetermining a shape of a luminal sample. The apparatus includes acatheter that is disposed within a strain-sensing sheath. Thestrain-sensing sheath is associated with strain-sensing molecules suchthat changes in the shape of the strain-sensing sheath lead to strain onthe sheath that can be detected spectroscopically. The catheter/sheathcombination may be inserted into a luminal structure such as an arteryand the shape of the artery is determined by measuring differences instrain along the sheath. In particular, a lens associated with thecatheter may be rotated inside the sheath while also being translated(e.g. using a pullback), producing a helical travel. While the lensmoves (e.g. helically) it collects data from the sheath (e.g. frommolecular spectroscopic data) that indicates strain and may also collectstructural information (e.g. OCT) which may be used to determine the 3Dshape of the luminal sample. The spectroscopic data from the sheath canbe combined with the structural information to determine the overallshape of the luminal sample, e.g. essentially producing a wireframemodel of the central axis of the luminal sample.

The strain-sensing molecules associated with the sheath are selectedbased on having a detectable spectral shift in response to changes instrain. Thus, in certain embodiments the strain-sensing sheath hasnanotubes (e.g. single-wall carbon nanotubes, SWCNTs) associated withthe sheath, where the nanotubes undergo a spectral shift as a result ofa change in strain.

To detect the spectral shift in the strain-sensing molecules, thecatheter has a lens (e.g. a ball lens) attached to its end, where thelens is configured to rotate and translate within the strain-sensingsheath. To facilitate rotation of the lens, the catheter in someembodiments is optically coupled to the structural optical system andthe molecular spectroscopic system using a rotary junction. The lens isconfigured to transmit light at an angle (e.g. a right angle) relativeto the long axis of the catheter so that light is emitted and collectedfrom the side walls of the sheath and the luminal structure into whichthe sheath has been inserted.

As the lens rotates and translates through the sheath, light is emittedfrom the lens and collected by the lens to collect data for determiningstrain and for determining structural information. The light from themolecular spectroscopic system is emitted by the lens and interacts withthe strain-sensing molecules associated with the sheath and lightreturned from the sheath (e.g. in the form of fluorescence) is collectedby the lens.

The returned light is analyzed spectroscopically to identify anyspectral shift(s) which are indicative of changes in strain. Strain canbe determined at two different locations along the axis of the sample(referred to as Z1 and Z2, e.g. see FIG. 10), for example by determiningstrain in an x-z plane and a y-z plane at each location. From thisinformation a local curvature of the catheter and sheath can bedetermined (with reference to calibration information). The molecularspectroscopic system may be based on fluorescence spectroscopy, Ramanspectroscopy, or absorption spectroscopy.

Light from the structural optical system (e.g. OCT) is also emittedthrough the lens as the lens/catheter moves (e.g. helically) through thesheath. Light returned from the sample is collected by the lens anddirected to the structural optical system. The returned light can beused to determine the position of the catheter, for example in an x-zplane and a y-z plane at each location Z1 and Z2. From this a localcurvature of the luminal structure can be determined relative to thecatheter (to the extent that the catheter does not exactly follow thecontours of the luminal structure).

The operation of the catheter and optical data collection may beperformed by one or more controllers, e.g. computer systems eachincluding one or more processors/microprocessors, memory, storage,input, output, and communications capabilities. The controller(s) maycontrol operations such as the rotation of the lens, emitting andcollecting light from the lens, and processing of data. Thecontroller(s) may be coupled to, e.g. may be in communication with, thestructural optical system and/or the molecular spectroscopic system inorder to perform functions related to these systems. In particular, thecontroller may carry out steps to perform operations according toembodiments disclosed herein.

In various embodiments the sheath includes a sheath wall. The sheathwall may be associated with strain-sensing molecules (e.g. SWCNTs). Invarious embodiments, the strain-sensing molecules may be on an insideface of the sheath wall, an outside face of the sheath wall, or may beembedded within the sheath wall. In other embodiments, thestrain-sensing molecules may be associated with one or more wires thatare then attached to the sheath wall, e.g. on the outside face. Incertain embodiments the strain-sensing sheath may be disposed withinanother, outer sheath (e.g. if the strain-sensing molecules are locatedon the outer wall of the strain-sensing sheath then by disposing thestrain-sensing sheath within another, outer sheath this keeps thestrain-sensing molecules away from the luminal sample, i.e. away fromthe body of the subject).

FIG. 15 is a flow chart of an example process 1500 for determining ashape of a luminal sample. The process 1500 includes a step of providinga catheter optically coupled to a structural imaging system and astrain-sensing system (step 1510). The catheter may include a lens andthe catheter may be disposed within a strain-sensing sheath such thatthe lens rotates and translates within the strain-sensing sheath. Theprocess 1500 may also include a step of determining a first position ofthe catheter relative to the luminal sample at a first location withinthe strain-sensing sheath (step 1520). This and other steps may becarried out by a controller coupled to the molecular spectroscopicsystem and the structural optical system. The process 1500 may furtherinclude a step of determining a second position of the catheter relativeto the luminal sample at a second location within the strain-sensingsheath (step 1530), where the first location is different from thesecond location. The process 1500 may also include steps of determininga first strain of the strain-sensing sheath at the first location (step1540) and determining a second strain of the strain-sensing sheath atthe second location (step 1550). The process 1500 may also include astep of determining a first local curvature of the luminal samplerelative to the catheter (step 1560) between the first location and thesecond location based on determining the first position and the secondposition of the catheter. The process 1500 may further include a step ofdetermining a second local curvature of the catheter (step 1570) betweenthe first location and the second location based on determining thefirst strain and the second strain of the strain-sensing sheath. Theprocess 1500 may additionally include a step of determining a thirdlocal curvature of the luminal sample (step 1580) between the firstlocation and the second location based on determining the first localcurvature and the second local curvature. Process 1500 of FIG. 15 may beused in conjunction with the methods and apparatus disclosed herein.

FIG. 16 is a flow chart of an example process 1600. The process 1600includes a step of providing a catheter being optically coupled to astrain-sensing system (step 1610). The catheter may include a lens andthe catheter may be disposed within a strain-sensing sheath such thatthe lens rotates and translates within the strain-sensing sheath. Theprocess 1600 may also include a step of determining a first strain ofthe strain-sensing sheath in an x-z plane and a y-z plane at a firstlocation (step 1620) within the strain-sensing sheath. This and othersteps may be carried out by a controller coupled to the molecularspectroscopic system. The process 1600 may further include a step ofdetermining a second strain of the strain-sensing sheath an x-z planeand a y-z plane at a second location (step 1630) within thestrain-sensing sheath, where the first location is different from thesecond location. The process 1600 may also include a step of determininga catheter curvature between the first location and the second location(step 1640) based on determining the first strain and the second strainof the strain-sensing sheath. Process 1600 of FIG. 16 may be used inconjunction with the methods and apparatus disclosed herein.

It will be apparent to those skilled in the art that numerous changesand modifications can be made in the specific embodiments of theinvention described above without departing from the scope of theinvention. Accordingly, the whole of the foregoing description is to beinterpreted in an illustrative and not in a limitative sense.

1. An apparatus, comprising: at least one optical waveguide that emitselectromagnetic radiation comprising a first electromagnetic radiationand a third electromagnetic radiation, a scanning arrangement that atleast one of rotates and translates to direct the electromagneticradiation, a strain-sensing sheath that at least partially encloses theat least one optical waveguide and the scanning arrangement, thestrain-sensing sheath comprising a strain-sensing system opticallycoupled to the at least one waveguide; and a controller coupled to thestrain-sensing system, the controller, using the strain-sensing system,to: determine a first strain of the strain-sensing sheath at a firstlocation by: transmitting the first electromagnetic radiation towardsthe strain-sensing sheath, obtaining a second electromagnetic radiationfrom the strain-sensing sheath based on fluorescence excited by thefirst electromagnetic radiation, and determining the first strain basedon obtaining the second electromagnetic radiation, and determine asecond strain of the strain-sensing sheath at a second location by:transmitting the third electromagnetic radiation towards thestrain-sensing sheath, obtaining a fourth electromagnetic radiation fromthe strain-sensing sheath based on fluorescence excited by the thirdelectromagnetic radiation, and determining the second strain based onobtaining the fourth electromagnetic radiation,  the first locationbeing different from the second location, and the controller further to:determine a curvature of the sheath between the first location and thesecond location based on determining the first strain and the secondstrain of the strain-sensing sheath.
 2. The apparatus of claim 1,further comprising a structural imaging system optically coupled to thesheath, wherein the strain-sensing sheath is disposed within ananatomical structure, and wherein the controller, using the structuralimaging system, is further to: determine a first position of the sheathrelative to the anatomical structure at the first location within thestrain-sensing sheath, determine a second position of the sheathrelative to the anatomical structure at the second location within thestrain-sensing sheath, determine a relative sample curvature of theanatomical structure with respect to the sheath between the firstlocation and the second location based on determining the first positionand the second position of the sheath, and determine an actual curvatureof the anatomical structure between the first location and the secondlocation based on determining the curvature of the sheath and therelative sample curvature.
 3. The apparatus of claim 2, wherein thewaveguide comprises an optical fiber.
 4. The apparatus of claim 3,wherein the optical fiber comprises a multi-clad optical fiber.
 5. Theapparatus of claim 2, wherein the sheath comprises a catheter sheath. 6.The apparatus of claim 2, wherein the anatomical structure comprises aluminal anatomical structure.
 7. The apparatus of claim 6, wherein theluminal anatomical structure comprises a blood vessel.
 8. The apparatusof claim 2, wherein the structural imaging system comprises an opticalcoherence tomography (OCT) system.
 9. The apparatus of claim 2, whereinthe strain-sensing sheath comprises a sheath wall.
 10. The apparatus ofclaim 9, wherein the strain-sensing sheath comprises strain-sensingmolecules associated with the sheath wall.
 11. The apparatus of claim10, wherein the strain-sensing molecules are associated with an insideface of the sheath wall.
 12. The apparatus of claim 10, wherein thestrain-sensing molecules are embedded within the sheath wall.
 13. Theapparatus of claim 10, wherein the strain-sensing molecules areassociated with an outside face of the sheath wall.
 14. The apparatus ofclaim 13, wherein the strain-sensing molecules are associated with aplurality of wires associated with the sheath wall.
 15. The apparatus ofclaim 2, wherein the strain-sensing sheath is disposed within anothersheath.
 16. The apparatus of claim 10, wherein the strain-sensingmolecules comprise single-walled carbon nanotubes (SWCNTs). 17.(canceled)
 18. The apparatus of claim 1, wherein the controller, whendetermining the first strain, is further to: determine the first strainbased on detecting a spectral shift in the second electromagneticradiation, and wherein the controller, when determining the secondstrain, is to: determine the second strain based on detecting a spectralshift in the fourth electromagnetic radiation.
 19. The apparatus ofclaim 1, wherein the controller, when determining the first strain, isfurther to: determine the first strain based on at least one offluorescence spectroscopy, Raman spectroscopy, or absorptionspectroscopy, and wherein the controller, when determining the secondstrain, is further to: determine the second strain based on at least oneof fluorescence spectroscopy, Raman spectroscopy, or absorptionspectroscopy.
 20. The apparatus of claim 2, wherein the strain-sensingsystem and the structural imaging system are optically coupled to thecatheter by a rotary junction.
 21. The apparatus of claim 2, wherein thecontroller is further to: determine a three-dimensional (3D) shape ofthe anatomical structure based on determining the actual curvature. 22.The apparatus of claim 1, wherein the optical waveguide comprises a lensat an end thereof.
 23. The apparatus of claim 22, wherein the scanningarrangement causes the lens to move helically through the strain-sensingsheath. 24-93. (canceled)